Administration of tert-butyl-4-hydroxyanisole or of two dithiolthiones to female CD-1 mice protected against the acute toxic effects of two hepatotoxic agents, acetaminophen and carbon tetrachloride. Reduced mortality of mice was observed following pretreatment with tert-butyl-4-hydroxyanisole or dithiolthiones. Pretreatment reduced or prevented hepatic glutathione depletion produced by these two hepatotoxic agents. Liver damage, i.e., as determined by serum transaminase and sorbitol dehydrogenase activities, was less after pretreatment with tert-butyl-4-hydroxyanisole or dithiolthiones. Administration of dithiolthiones resulted in increased (from four- to over six-fold) activities of liver glutathione-S-transferases.
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| http://dx.doi.org/10.1002/hep.1840030608 | DOI Listing |
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Early events in the induction of rat hepatic UDP-glucuronosyltransferases, glutathione S-transferase, and microsomal epoxide hydrolase by 1,7-phenanthroline: comparison with oltipraz, tert-butyl-4-hydroxyanisole, and tert-butylhydroquinone.
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September 2000
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112-5820, USA.
Several classes of compounds are able to induce a spectrum of drug-metabolizing enzymes without inducing cytochrome P450s. Examples include antioxidants such as tert-butyl-4-hydroxyanisole and its metabolite tert-butylhydroquinone, dithiolthiones such as oltipraz, and N-heterocycles such as 1,7-phenanthroline. The events associated with induction of UDP-glucuronosyltransferases (UGT), glutathione S-transferases, and microsomal epoxide hydrolase after a single oral dose of these agents have been compared.
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